文章：

FBXO4通过靶向Mcl-1降解抑制肺癌细胞存活

FBXO4 inhibits lung cancer cell survival by targeting Mcl-1 for degradation 

原文发布日期：2017-08-04 

英文摘要：

Mcl-1 (myeloid cell leukemia 1) is a prosurvival member of the Bcl-2 family and plays a critical role in cell survival by suppressing apoptosis through inhibiting the activity of proapoptotic proteins. It has been reported that Mcl-1 is frequently overexpressed in lung cancer. However, the exact molecular mechanism underlying Mcl-1 elevation in lung cancer is largely unknown. Here, we reported that Mcl-1 protein levels inversely correlate with FBXO4 expression, but not other F-box proteins examined, in lung cancer cell lines and lung cancer patient samples. Mechanically, FBXO4 is the E3 ubiquitin ligase to interact with and promote Mcl-1 ubiquitination and degradation. As a result, knockdown of Fbxo4 dramatically elevates Mcl-1 protein levels and increases cell survival and resistance to chemotherapeutic drugs, whereas ectopic expression of FBXO4 displays opposite phenotypes. Therefore, our study suggests that the protein stability of Mcl-1 is governed by FBXO4, which plays an important role in cell survival and chemotherapy for lung cancer.

摘要翻译： 

Mcl-1（髓样细胞白血病因子1）是Bcl-2家族中的促存活成员，通过抑制促凋亡蛋白的活性来阻止细胞凋亡，在细胞存活中起关键作用。据报道，Mcl-1在肺癌中经常过度表达，但其在肺癌中表达升高的具体分子机制尚不明确。本研究发现，在肺癌细胞系和肺癌患者样本中，Mcl-1蛋白水平与FBXO4表达呈负相关，而与其他检测的F-box蛋白无此关联。从机制上讲，FBXO4作为E3泛素连接酶与Mcl-1相互作用，促进其泛素化与降解。敲低Fbxo4会显著升高Mcl-1蛋白水平，增强细胞存活能力和对化疗药物的耐药性；而异位表达FBXO4则呈现相反表型。因此，本研究揭示FBXO4通过调控Mcl-1蛋白稳定性，在肺癌细胞存活及化疗反应中发挥重要作用。

原文链接：

FBXO4 inhibits lung cancer cell survival by targeting Mcl-1 for degradation